Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMIFCY2)

Drug Name

H3B-6545 Drug Info

Synonyms

JPFTZIJTXCHJNE-HMOQVRKWSA-N; SCHEMBL18261010; HY-112596; CS-0047714; (2e)-N,N-dimethyl-4-{[2-({5-[(1z)-4,4,4-trifluoro-1-(3-fluoro-1h-indazol-5-yl)-2-phenylbut-1-en-1-yl]pyridin-2-yl}oxy)ethyl]amino}but-2-enamide

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 1/2	[1]

Cross-matching ID

PubChem CID: 124091040
TTD Drug ID: DMIFCY2
INTEDE Drug ID: DR1799

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Antagonist	[2]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Phase 1	[3]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Phase 1	[3]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Phase 1	[3]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Phase 1	[3]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Phase 1	[3]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Phase 1	[3]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Phase 1	[3]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Phase 1	[3]
Cytochrome P450 2J2 (CYP2J2)	DERSX5P	CP2J2_HUMAN	Phase 1	[3]

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The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Estrogen receptor (ESR)	DTT	ESR1	3.728	3.17	4.897	4.505
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	9.791	3.744	3.413	1.609
Cytochrome P450 2J2 (CYP2J2)	DME	CYP2J2	7.706	6.315	4.621	7.65
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	10.036	5.779	6.508	6.481
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	10.08	7.207	5.403	9.211
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	7.867	5.142	5.52	7.08
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	3.307	5.005	3.921	5.327
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	11.76	5.931	6.164	9.423
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	11.692	6.58	4.984	9.089

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease

Breast cancer

ICD Disease Classification

2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	9.78E-01	-3.38E-03	-5.71E-02
Cytochrome P450 2J2 (CYP2J2)	DME	CYP2J2	6.32E-01	-4.03E-02	-1.63E-01
Cytochrome P450 2B6 (CYP2B6)	DME	CYP2B6	3.97E-02	-1.72E-01	-9.29E-01
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	9.96E-01	-7.53E-02	-5.68E-01
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	5.82E-01	-6.00E-02	-2.69E-01
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	3.44E-01	-1.85E-01	-5.25E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	7.95E-01	-7.47E-02	-2.45E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	9.09E-01	-9.26E-02	-3.68E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	9.85E-01	2.24E-02	7.33E-02

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	ClinicalTrials.gov (NCT03250676) Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer. U.S. National Institutes of Health.
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	Nonclinical pharmacokinetics and in vitro metabolism of H3B-6545, a novel selective ERalpha covalent antagonist (SERCA). Cancer Chemother Pharmacol. 2019 Jan;83(1):151-160.